(1) Field of the Invention
The present invention relates to a process for producing organic substituted aromatic or heteroaromatic compounds including biaryl and biheteroaryl compounds in a two-step reaction. In the first step, the aromatic or heteroaromatic compound is borylated in a reaction comprising a borane or diborane reagent (any boron reagent where the boron reagent contains a B—H, B—B or B—Si bond) and an iridium or rhodium catalytic complex. In the second step, a metal catalyst catalyzes the formation of the organic substituted aromatic or heteroaromatic compound from the borylated compound and an electrophile such as an organic or aryl halide, triflate (OSO2CF3), or nonaflate (OSO2C4F9). The steps in the process can be performed in a single reaction vessel or in separate reaction vessels. The present invention also provides a process for synthesis of complex polyphenylenes starting from halogenated aromatic compounds.
(2) Description of Related Art
Carbon-carbon bonds are the molecular “bricks and mortar” from which diverse architectures in living organisms and man-made materials are constructed. As the field of organic chemistry has evolved, numerous methods for carbon-carbon bond construction have been developed, ranging from classic examples, like the Diels-Alder reaction, to more recent metal-catalyzed processes such as olefin polymerizations and metatheses.
Substituted aromatic, and their heteroaromatic analogs, are abundant in natural and in synthetic-materials. Consequently, controlled methods for linking aromatic rings via C—C sigma bonds have long been pursued by organic chemists. Activity in this regard intensified in the late 1970's during which Pd catalyzed methods for C—C bond construction emerged (Diederich and Stang, Metal-Catalyzed Cross-Coupling Reactions. Wiley-VCH, New York (1998)). Notably, the Pd catalyzed coupling of an arylboronic acid and an aryl halide disclosed by Miyaura and Suzuki,
(Y=OH; X=halide) has become a method of choice for preparing biaryls since it is performed under mild conditions, tolerant of diverse functionality, and highly selective (Miyaura et al., Synth. Commun. 11: 513–519 (1981)). Subsequent developments in metal-catalyzed cross-couplings of organoboron compounds and organic halides have yielded practical C—C bond forming strategies that complement existing methodology (Suzuki, Organomet. Chem. 576; 147–168 (1999)). Today the Miyaura-Suzuki reaction is routinely applied in high-throughput screening for drug discovery (Sammelson and Kurth, Chem. Rev. 101: 137–202 (2001)), in the final steps of convergent natural product syntheses (Chemler and Danishefsky, Org. Lett. 2: 2695–2698 (2000)), and in the synthesis of conjugated organic materials (Schlüter, J. Polym. Sci. A-Polym. Chem. 39: 1533–1556 (2001)).
Arylboron reagents are typically synthesized in a multi-step process such as that shown below.
Shorter routes that avoid undesirable halogenated aromatic intermediates would be attractive. Towards this end, theoretical estimates of B—H and B—C bond enthalpies gave credence to organoborane synthesis via the thermal dehydrogenative coupling of B—H and C—H bonds as shown below (Rablen et al., J. Am. Chem. Soc. 116: 4121–4122 (1994)).
Some key steps in putative catalytic cycles for this process had been established with Hartwig's (Waltz et al., J. Am. Chem. Soc. 117: 11357–11358 (1995); Waltz and Hartwig, Science 277: 211–213 (1997)) and Marder's reports of stoichiometric borylations of arenes, alkenes, and alkanes by metal boryl complexes (M-BR2). Although arene activation products were not mentioned, small peaks in the GC-MS trace with masses consistent with toluene borylation products were assigned in the Supplementary Material to Nguyen et al., Am. Chem. Soc. 115, 9329–9330 (1993).
While Hartwig has developed elegant photochemical methods for hydrocarbon borylation using catalytic amounts of metal complexes (Chen and Hartwig, Angew. Chem. Int. Ed. 38: 3391–3393 (1999)), thermal, catalytic borylations of unactivated hydrocarbons had not been documented prior to our report in 1999 (Iverson and Smith, III, J. Am. Chem. Soc. 121: 7696–7697 (1999)). Since then, borylation of aliphatic and alkyl branched alicyclic hydrocarbons at a primary C—H hydrocarbon bond under thermal conditions using a rhodium catalytic complex which includes an electron donor ligand was disclosed in WO 01/64689 A1 and U.S. Patent Application No. 0039349 A1, both to Chen et al., and borylation of cyclic hydrocarbons at a secondary or aromatic C—H cyclic hydrocarbon bond using the above rhodium catalytic complex was disclosed in WO 01/64688 A1 to Chen et al.
Currently, because C—C coupling of a hydrocarbon requires a multi-step process to produce a borylated hydrocarbon, which is then reacted with a hydrocarbon halide to couple the hydrocarbons, it would be desirable to have a process wherein the borylation and the C—C coupling are performed in fewer steps or in the same reaction vessel, or both. Therefore, a need remains for a process for C—C coupling of hydrocarbons which can be performed in fewer steps and preferably, in the same reaction vessel.